CAB39 (calcium binding protein 39) is a scaffold protein that functions as a critical regulator of multiple signaling pathways. Structurally, CAB39 comprises seven helical repeats and acts as a component of kinase-activating complexes 1. Primary functionally, CAB39 stabilizes and activates the tumor suppressor kinase STK11/LKB1 and promotes activities of STE20-family kinases including SPAK and OSR1 2, with studies showing CAB39 can enhance SPAK activity up to 100-fold 2. Mechanistically, CAB39 operates through multiple pathways: the LKB1-AMPK-LC3 axis regulating mitochondrial autophagy 3, the AMPK-Nrf2 cascade for antioxidant responses 4, the NF-κB pathway promoting epithelial-mesenchymal transition 5, and the WNK-SPAK-OSR1 axis controlling renal ion transport 2. CAB39 expression is negatively regulated by miR-107, miR-451, and miR-451a across multiple cancer types 4, 6, 7, 8. Disease relevance: CAB39 is overexpressed in bladder, pancreatic, and esophageal cancers, correlating with poor prognosis 5, 7. Notably, elevated CAB39 promotes cisplatin resistance in bladder cancer through enhanced autophagy 3 and chemoresistance in colorectal cancer via the AMPK-mTOR pathway 6. Clinically, CAB39 represents a promising therapeutic target. Autophagy inhibitors combined with chemotherapy significantly enhanced tumor killing 3, and small-molecule CAB39 inhibitors show therapeutic potential for managing hypertension and chemoresistance 2.